HAND1_MOUSE
ID HAND1_MOUSE Reviewed; 216 AA.
AC Q64279; Q61099;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Heart- and neural crest derivatives-expressed protein 1;
DE AltName: Full=Extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1;
DE Short=eHAND;
DE AltName: Full=Helix-loop-helix transcription factor expressed in extraembryonic mesoderm and trophoblast;
DE AltName: Full=Thing-1;
DE Short=Th1;
GN Name=Hand1; Synonyms=Ehand, Hxt, Thing1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC STRAIN=NIH Swiss; TISSUE=Embryo;
RX PubMed=7791788; DOI=10.1128/mcb.15.7.3813;
RA Hollenberg S.M., Sternglanz R., Cheng P.F., Weintraub H.;
RT "Identification of a new family of tissue-specific basic helix-loop-helix
RT proteins with a two-hybrid system.";
RL Mol. Cell. Biol. 15:3813-3822(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RC TISSUE=Embryo;
RX PubMed=7649392; DOI=10.1006/dbio.1995.1245;
RA Cserjesi P., Brown D., Lyons G.E., Olson E.N.;
RT "Expression of the novel basic helix-loop-helix gene eHAND in neural crest
RT derivatives and extraembryonic membranes during mouse development.";
RL Dev. Biol. 170:664-678(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=129/Sv; TISSUE=Embryoid bodies;
RX PubMed=7671815; DOI=10.1242/dev.121.8.2513;
RA Cross J.C., Flannery M.L., Blanar M.A., Steingrimsson E., Jenkins N.A.,
RA Copeland N.G., Rutter W.J., Werb Z.;
RT "Hxt encodes a basic helix-loop-helix transcription factor that regulates
RT trophoblast cell development.";
RL Development 121:2513-2523(1995).
RN [4]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=9500551; DOI=10.1038/ng0398-271;
RA Riley P., Anson-Cartwright L., Cross J.C.;
RT "The Hand1 bHLH transcription factor is essential for placentation and
RT cardiac morphogenesis.";
RL Nat. Genet. 18:271-275(1998).
RN [5]
RP SUBUNIT.
RX PubMed=10924525; DOI=10.1074/jbc.m005888200;
RA Firulli B.A., Hadzic D.B., McDaid J.R., Firulli A.B.;
RT "The basic helix-loop-helix transcription factors dHAND and eHAND exhibit
RT dimerization characteristics that suggest complex regulation of function.";
RL J. Biol. Chem. 275:33567-33573(2000).
RN [6]
RP FUNCTION, INTERACTION WITH SOX15, AND DEVELOPMENTAL STAGE.
RX PubMed=16759287; DOI=10.1111/j.1432-0436.2006.00070.x;
RA Yamada K., Kanda H., Tanaka S., Takamatsu N., Shiba T., Ito M.;
RT "Sox15 enhances trophoblast giant cell differentiation induced by Hand1 in
RT mouse placenta.";
RL Differentiation 74:212-221(2006).
RN [7]
RP SUBCELLULAR LOCATION, INTERACTION WITH MDFIC, PHOSPHORYLATION AT THR-107
RP AND SER-109, AND MUTAGENESIS OF THR-107 AND SER-109.
RX PubMed=17891141; DOI=10.1038/ncb1633;
RA Martindill D.M.J., Risebro C.A., Smart N., Franco-Viseras Mdel M.,
RA Rosario C.O., Swallow C.J., Dennis J.W., Riley P.R.;
RT "Nucleolar release of Hand1 acts as a molecular switch to determine cell
RT fate.";
RL Nat. Cell Biol. 9:1131-1141(2007).
CC -!- FUNCTION: Transcription factor that plays an essential role in both
CC trophoblast giant cell differentiation and in cardiac morphogenesis
CC (PubMed:9500551, PubMed:16759287). Binds the DNA sequence 5'-NRTCTG-3'
CC (non-canonical E-box) (PubMed:7791788). Acts as a transcriptional
CC repressor of SOX15 (PubMed:16759287). In the adult, could be required
CC for ongoing expression of cardiac-specific genes (By similarity).
CC {ECO:0000250|UniProtKB:O96004, ECO:0000269|PubMed:16759287,
CC ECO:0000269|PubMed:7791788, ECO:0000269|PubMed:9500551}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Forms homodimers and heterodimers with TCF3 gene products E12
CC and E47, HAND2 and HEY1, HEY2 and HEYL (hairy-related transcription
CC factors). Interacts with MDFIC. Interacts with SOX15; the interaction
CC enhances HAND1-induced differentiation of trophoblast giant cells
CC (PubMed:16759287). {ECO:0000269|PubMed:10924525,
CC ECO:0000269|PubMed:16759287, ECO:0000269|PubMed:17891141}.
CC -!- INTERACTION:
CC Q64279; Q64279: Hand1; NbExp=2; IntAct=EBI-81361, EBI-81361;
CC Q64279; Q61039: Hand2; NbExp=3; IntAct=EBI-81361, EBI-81388;
CC Q64279; P15806: Tcf3; NbExp=2; IntAct=EBI-81361, EBI-81370;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:17891141}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:17891141}. Note=Interaction with MDFIC sequesters
CC it into the nucleolus, preventing the transcription factor activity.
CC Phosphorylation by PLK4 disrupts the interaction with MDFIC and
CC releases it from the nucleolus, leading to transcription factor
CC activity.
CC -!- TISSUE SPECIFICITY: Smooth muscle cells of the gut and adrenal tissue.
CC -!- DEVELOPMENTAL STAGE: Present as a maternal transcript in the egg as
CC well as during cleavage development before blastocyst formation. At 7.5
CC dpc, strongly expressed in all trophoblast cells (PubMed:16759287).
CC Expression seen in the ectoplacental cone and extraembryonic mesodermal
CC components of the amnion, allantois and visceral yolk sac. This high
CC extraembryonic expression persists in the embryonic component of the
CC placenta throughout development. In the embryo, expressed at 7.75 dpc
CC in the lateral mesoderm along the entire length of the embryo as well
CC as throughout the precardiogenic mesoderm. At 8.0 dpc, in the
CC developing heart, expression becomes restricted to the rostral and
CC caudal regions of the straight heart tube, which are fated to form the
CC conotruncus and left ventricle, respectively. Symmetric expression is
CC observed along the left-right axis in the caudal heart tube and lateral
CC mesoderm. As cardiac looping occurs, the interrupted anterior-posterior
CC patterning is maintained with expression in the future left, but not
CC right ventricle. Expressed in the myocardium, but not in the
CC endocardium, and specifically on the greater curvature of the looping
CC heart which is opposed to the pericardium. After day 10.5 dpc, the high
CC cardiac expression level declines abruptly. By 13.5 dpc, expression in
CC the heart is restricted to the regions of valve formation. Besides the
CC heart, expression becomes detectable in the gut at 9.0 dpc. At 10.0
CC dpc, expressed also in the lateral mesoderm and in the neural crest-
CC derived branchial arches. At 10.5 dpc prominent expression in the gut,
CC pharyngeal arches and in sympathetic ganglion primordia. At that stage,
CC a low level of transient expression is seen in the distal posterior
CC region of the limb bud. At 12 dpc expressed in the conceptus
CC trophoblast giant cell layer in the placenta (PubMed:16759287). At 13.5
CC dpc expressed in neural crest derivatives, with abundant expression in
CC the autonomic nervous system and adrenal medulla.
CC {ECO:0000269|PubMed:16759287, ECO:0000269|PubMed:7649392,
CC ECO:0000269|PubMed:9500551}.
CC -!- PTM: Phosphorylation by PLK4 disrupts the interaction with MDFIC and
CC leads to translocation into the nucleoplasm, allowing dimerization and
CC transcription factor activity. {ECO:0000269|PubMed:17891141}.
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DR EMBL; U21226; AAA86887.1; -; mRNA.
DR EMBL; S79216; AAB35104.1; -; mRNA.
DR EMBL; U43714; AAA86273.1; -; mRNA.
DR CCDS; CCDS24721.1; -.
DR RefSeq; NP_032239.1; NM_008213.2.
DR AlphaFoldDB; Q64279; -.
DR SMR; Q64279; -.
DR BioGRID; 200204; 7.
DR DIP; DIP-455N; -.
DR IntAct; Q64279; 6.
DR STRING; 10090.ENSMUSP00000046999; -.
DR iPTMnet; Q64279; -.
DR PhosphoSitePlus; Q64279; -.
DR PaxDb; Q64279; -.
DR PRIDE; Q64279; -.
DR ProteomicsDB; 271389; -.
DR Antibodypedia; 16446; 381 antibodies from 35 providers.
DR DNASU; 15110; -.
DR Ensembl; ENSMUST00000036917; ENSMUSP00000046999; ENSMUSG00000037335.
DR Ensembl; ENSMUST00000160392; ENSMUSP00000124951; ENSMUSG00000037335.
DR GeneID; 15110; -.
DR KEGG; mmu:15110; -.
DR UCSC; uc007jaf.1; mouse.
DR CTD; 9421; -.
DR MGI; MGI:103577; Hand1.
DR VEuPathDB; HostDB:ENSMUSG00000037335; -.
DR eggNOG; KOG4029; Eukaryota.
DR GeneTree; ENSGT00940000161111; -.
DR HOGENOM; CLU_119591_0_0_1; -.
DR InParanoid; Q64279; -.
DR OMA; YFQSWVL; -.
DR OrthoDB; 1449816at2759; -.
DR PhylomeDB; Q64279; -.
DR TreeFam; TF315153; -.
DR BioGRID-ORCS; 15110; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Hand1; mouse.
DR PRO; PR:Q64279; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q64279; protein.
DR Bgee; ENSMUSG00000037335; Expressed in ectoplacental cone and 106 other tissues.
DR ExpressionAtlas; Q64279; baseline and differential.
DR Genevisible; Q64279; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:MGI.
DR GO; GO:0043425; F:bHLH transcription factor binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IGI:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0001221; F:transcription coregulator binding; IPI:BHF-UCL.
DR GO; GO:0001525; P:angiogenesis; IMP:MGI.
DR GO; GO:0003218; P:cardiac left ventricle formation; ISO:MGI.
DR GO; GO:0003219; P:cardiac right ventricle formation; ISO:MGI.
DR GO; GO:0060411; P:cardiac septum morphogenesis; ISO:MGI.
DR GO; GO:0060536; P:cartilage morphogenesis; IGI:MGI.
DR GO; GO:0030154; P:cell differentiation; IGI:MGI.
DR GO; GO:0001709; P:cell fate determination; NAS:UniProtKB.
DR GO; GO:0061371; P:determination of heart left/right asymmetry; IMP:MGI.
DR GO; GO:0032502; P:developmental process; IBA:GO_Central.
DR GO; GO:0035050; P:embryonic heart tube development; IMP:MGI.
DR GO; GO:0003144; P:embryonic heart tube formation; IMP:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0001947; P:heart looping; IMP:MGI.
DR GO; GO:0003007; P:heart morphogenesis; TAS:BHF-UCL.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0060485; P:mesenchyme development; IGI:MGI.
DR GO; GO:0001707; P:mesoderm formation; IMP:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:1903026; P:negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IGI:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0001829; P:trophectodermal cell differentiation; IEA:Ensembl.
DR GO; GO:0060707; P:trophoblast giant cell differentiation; IDA:MGI.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IMP:MGI.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Activator; Developmental protein; DNA-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..216
FT /note="Heart- and neural crest derivatives-expressed
FT protein 1"
FT /id="PRO_0000127185"
FT DOMAIN 94..146
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 53..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 165..203
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 165..183
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 107
FT /note="Phosphothreonine; by PLK4"
FT /evidence="ECO:0000269|PubMed:17891141"
FT MOD_RES 109
FT /note="Phosphoserine; by PLK4"
FT /evidence="ECO:0000269|PubMed:17891141"
FT MUTAGEN 107
FT /note="T->A: Remains exclusively in the nucleolus; when
FT associated with A-109."
FT /evidence="ECO:0000269|PubMed:17891141"
FT MUTAGEN 107
FT /note="T->D: Adopts a nucleus-wide distribution; when
FT associated with D-109."
FT /evidence="ECO:0000269|PubMed:17891141"
FT MUTAGEN 109
FT /note="S->A: Remains exclusively in the nucleolus; when
FT associated with A-107."
FT /evidence="ECO:0000269|PubMed:17891141"
FT MUTAGEN 109
FT /note="S->D: Adopts a nucleus-wide distribution; when
FT associated with D-107."
FT /evidence="ECO:0000269|PubMed:17891141"
FT CONFLICT 6
FT /note="S -> R (in Ref. 3; AAA86273)"
FT /evidence="ECO:0000305"
FT CONFLICT 19
FT /note="P -> A (in Ref. 3; AAA86273)"
FT /evidence="ECO:0000305"
FT CONFLICT 131
FT /note="S -> P (in Ref. 3; AAA86273)"
FT /evidence="ECO:0000305"
FT CONFLICT 149
FT /note="V -> A (in Ref. 3; AAA86273)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="A -> V (in Ref. 3; AAA86273)"
FT /evidence="ECO:0000305"
FT CONFLICT 187
FT /note="S -> G (in Ref. 3; AAA86273)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="Q -> K (in Ref. 3; AAA86273)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 216 AA; 23806 MW; 307B14BB835833F1 CRC64;
MNLVGSYAHH HHHHHSHPPH PMLHEPFLFG PASRCHQERP YFQSWLLSPA DAAPDFPAGG
PPPTTAVAAA AYGPDARPSQ SPGRLEALGS RLPKRKGSGP KKERRRTESI NSAFAELREC
IPNVPADTKL SKIKTLRLAT SYIAYLMDVL AKDAQAGDPE AFKAELKKTD GGRESKRKRE
LPQQPESFPP ASGPGEKRIK GRTGWPQQVW ALELNQ
